Introduction In guided bone regeneration, the use of bone substitutes protected by resorbable barrier membranes is suggested for the treatment of bone defects. Sprouting of vessels from surrounding local bone and periosteum into such regenerated areas is an important factor for osteogenesis. However, isolating the grafted area from the overlying periosteum with a barrier membrane may affect the revascularization of the site, thus compromising new bone formation. Aim The aim of this experimental study was to perform a comparative evaluation of neoangiogenesis in bone defects filled with a bone graft and covered with a resorbable barrier membrane or a collagen fleece. Method Eighteen 2.5-3.5 kg weighing New Zealand white rabbits were used. Two circular bicortical bone defects (8 mm in diameter) were created in the calvaria of the animals and subsequently filled with a deproteinized bovine bone mineral ([DBBM]; Bio-Oss®, Geistlich Pharma AG, Wolhusen, Switzerland). One grafted defect was covered with a resorbable collagen membrane (Bio-Guide®, Geistlich Pharma AG) (group A), while the other site was covered by a collagen fleece (Jason® collagen fleece, Botiss Biomaterials GmbH, Zossen, Germany) (group B). The rabbits were divided into three study groups (7, 14, and 28 days), each containing six animals. Specimens were taken, and histological and immunohistological analyses were carried out concerning the number of newly formed vessels. Results All specimens showed uneventful bone formation at 28 days. There was a statistically significant difference in the number of blood vessels for the collagen fleece group at all time periods (7, 14, and 28 days). Conclusions The results of this study indicate that covering a bone graft with a quickly resorbable biomaterial (collagen fleece) allows for a greater degree of neoangiogenesis compared to a resorbable collagen barrier membrane.

Sigmoid sinus wall anomalies (SSWA) are closely linked to venous pulsatile tinnitus (PT). This study aims to demonstrate that SSWA develops progressively rather than being congenital.

We retrospectively analyzed 42 PT patients with SSWA who had at least two non-operative CT scans at our clinic. CT images were longitudinally assessed to track SSWA progression, while MRI and Doppler ultrasound evaluated transverse sinus stenosis and venous hemodynamics. Changes in PT perception were tracked using the tinnitus handicap inventory (THI) questionnaire.

Among the 42 SSWA patients, 12 (28.6%) exhibited progression. Anastomosis between diploic vein and diverticulum was significantly higher compared to the dehiscence cohort (p < 0.01). Within the diverticulum group, seven individuals (30.4%) experienced enlargement, with a mean diverticular wall expansion of 5.9% ± 11.4%. Progressive erosion was observed in two cases (12.5%) in the dehiscence cohort, with a mean sigmoid plate erosion of 3.8% ± 10.1%. In cases progressing from dehiscence to diverticulum, three subjects transitioned, with a mean sigmoid sinus wall length expansion of 43.8% ± 31.9%. SSWA progression showed a significant negative correlation with QBILATERAL (r = -0.857, p = 0.014), and there was a significant difference between initial and revisit THI scores (p < 0.01).

SSWA can undergo morphological progression, indicating it is a progressive clinical condition rather than congenital.

4 Laryngoscope, 134:4707-4715, 2024.

Acquired cranial defects are a prevalent condition in neurosurgery and call for cranioplasty, where the missing or defective cranium is replaced by an implant. Nevertheless, the biomaterials in current clinical applications are hardly exempt from long-term safety and comfort concerns. An appealing solution is regenerative cranioplasty, where biomaterials with/without cells and bioactive molecules are applied to induce the regeneration of the cranium and ultimately repair the cranial defects. This review examines the current state of research, development, and translational application of regenerative cranioplasty biomaterials and discusses the efforts required in future research. The first section briefly introduced the regenerative capacity of the cranium, including the spontaneous bone regeneration bioactivities and the presence of pluripotent skeletal stem cells in the cranial suture. Then, three major types of biomaterials for regenerative cranioplasty, namely the calcium phosphate/titanium (CaP/Ti) composites, mineralised collagen, and 3D-printed polycaprolactone (PCL) composites, are reviewed for their composition, material properties, and findings from clinical trials. The third part discusses perspectives on future research and development of regenerative cranioplasty biomaterials, with a considerable portion based on issues identified in clinical trials. This review aims to facilitate the development of biomaterials that ultimately contribute to a safer and more effective healing of cranial defects.

Bone defects of the craniofacial skeleton are often associated with aesthetic and functional impairment as well as loss of protection to intra- and extracranial structures. Solid titanium plates and individually adapted bone cements have been the materials of choice, but may lead to foreign-body reactions and insufficient osseointegration. In contrast, porous scaffolds are thought to exhibit osteoconductive properties to support bone ingrowth. Here, we analyse in critical size defects of the calvaria in sheep whether different bone replacement materials may overcome those remaining challenges. In a critical size defect model, bilateral 20 × 20 × 5-mm craniectomies were performed on either side of the sagittal sinus in 24 adult female blackheaded sheep. Bony defects were randomised to one of five different bone replacement materials (BRMs): titanium scaffold, biodegradable poly(d,l-lactic acid) calcium carbonate scaffold (PDLLA/CC), polyethylene 1 (0.71 mm mean pore size) or 2 (0.515 mm mean pore size) scaffolds and polymethyl methacrylate (PMMA)-based bone cement block. Empty controls (n = 3) served as references. To evaluate bone growth over time, three different fluorochromes were administered at different time points. At 3, 6 and 12 months after surgery, animals were sacrificed and the BRMs and surrounding bone analysed by micro-CT and histomorphometry. The empty control group verified that the calvaria defect in this study was a reliable critical size defect model. Bone formation in vivo was detectable in all BRMs after 12 months by micro-CT and histomorphometric analysis, except for the non-porous PMMA group. A maximum of bone formation was detected in the 12-months group for titanium and PDLLA/CC. Bone formation in PDLLA/CC starts to increase rapidly between 6 and 12 months, as the BRM resorbs over time. Contact between bone and BRM influenced bone formation inside the BRM. Empty controls exhibited bone formation solely at the periphery. Overall, porous BRMs offered bone integration to different extent over 12 months in the tested calvaria defect model. Titanium and PDLLA/CC scaffolds showed remarkable osseointegration properties by micro-CT and histomorphometric analysis. PDLLA/CC scaffolds degraded over time without major residues. Pore size influenced bone ingrowth in polyethylene, emphasising the importance of porous scaffold structure.

Tendon-bone insertion injuries such as rotator cuff and anterior cruciate ligament injuries are currently highly common and severe. The key method of treating this kind of injury is the reconstruction operation. The success of this reconstructive process depends on the ability of the graft to incorporate into the bone. Recently, there has been substantial discussion about how to enhance the integration of tendon and bone through biological methods. Stem cells like bone marrow mesenchymal stem cells (MSCs), tendon stem/progenitor cells, synovium-derived MSCs, adipose-derived stem cells, or periosteum-derived periosteal stem cells can self-regenerate and potentially differentiate into different cell types, which have been widely used in tissue repair and regeneration. Thus, we concentrate in this review on the current circumstances of tendon-bone healing using stem cell therapy.

Traditional two-dimensional histological sections and microcomputed tomography remain to be the major tools for studying craniofacial bones despite the complicated spatial organization of craniofacial organs. Recently, our laboratory developed the Poly(Ethylene Glycol) Associated Solvent System (PEGASOS) tissue clearing method, which can efficiently render hard tissues, including bones and teeth fully transparent without losing endogenous fluorescent signals. Complete tissue transparency enables us to acquire three-dimensional (3D) images of craniofacial bone vasculature, osteogenesis utilizing various labeling strategies, thus to investigate the spatial relationship among different tissues during postnatal craniofacial development. We found out that during the early stage of postnatal development, craniofacial osteogenesis occurs throughout the entire craniofacial bones, including the periosteum, dura, bone marrow, and suture. After 3-4 weeks, craniofacial osteogenesis is gradually restricted to the suture region and remaining bone marrow space. Similarly, craniofacial bone vasculature gradually restricts to the suture region. Osteogenesis is spatially associated with vasculature during the entire postnatal development. Importantly, we demonstrated that in adult calvarial bones, Gli1+ mesenchymal stem cells were also spatially associated with the vasculature. These findings indicate that craniofacial bones share similar osteogenesis mechanism as the long bone despite their distinct osteogenic mechanisms. In addition, the PEGASOS tissue clearing method-based 3D imaging technique is a useful new tool for craniofacial research.

Standardized and reproducible animal models are required for the assessment of bone healing mediated by biomaterials, cells, and drugs. Among the available bone-fractured models, calvarial defect is a simple and adequate option when researchers investigate intra-membranous bone formation and the influence of their regenerative solutions. However, the conventional surgical tools required to perform calvaria osteotomies (i.e., trephine bur mounted on a dental handpiece, DS) can affect the subjacent tissues of the skull, which are the dura mater and the brain. We hypothesized that the quality of the calvaria defect and the preservation of underlying tissues can be improved using a novel Anspach high-speed drill with a Codman Neuro Disposable Perforator handheld (ACP). Using a rabbit cadaveric models, we performed calvarial defects with either conventional DS or the ACP system, and showed that both techniques allowed to create standardized defects with circular geometry. We demonstrated that the ACP had clear benefices in terms of DM preservation and absence of exothermic reaction upon drilling. Even though this comparative work was conducted on cadaver, it is of substantial importance as it introduces a novel technique, easily applicable to investigate calvaria bone healing, which brings clear advantages compared to the conventional dental station. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 9999:1-9, 2019.

Meningeal inflammation and encapsulation of neural electrode arrays is a leading cause of device failure, yet little is known about how it develops over time or what triggers it. This work characterizes the dynamic changes of meningeal inflammatory cells and collagen-I in order to understand the meningeal tissue response to neural electrode implantation. We use in vivo two-photon microscopy of CX3CR1-GFP mice over the first month after electrode implantation to quantify changes in inflammatory cell behavior as well as meningeal collagen-I remodeling. We define a migratory window during the first day after electrode implantation hallmarked by robust inflammatory cell migration along electrodes in the meninges as well as cell trafficking through meningeal venules. This migratory window attenuates by 2 days post-implant, but over the next month, the meningeal collagen-I remodels to conform to the surface of the electrode and thickens. This work shows that there are distinct time courses for initial meningeal inflammatory cell infiltration and meningeal collagen-I remodeling. This may indicate a therapeutic window early after implantation for modulation and mitigation of meningeal inflammation.

Frontofacial monobloc advancement creates a communication between the anterior cranial fossa and nasal cavities. To tackle this issue, transorbital pericranial pedicled flaps are routinely performed in the authors' center. This study aimed to assess the postoperative ossification of the anterior skull base and pedicled flaps following frontofacial monobloc advancement, and to identify factors influencing this ossification.

Measurements of the skull base only and of the ossified pedicled flaps together with the skull base were performed on computed tomographic scans at the nasofrontal and the nasoethmoid frontal junctions. The total thickness of the skull vault was measured and a qualitative defect score for the anterior skull base was computed.

Twenty-two patients who underwent frontofacial monobloc advancement at a median age of 3.1 years (range, 1.9 to 3.6 years) were included: 14 with Crouzon, five with Pfeiffer, and three with Apert syndrome. One year and 5 years after surgery, the distraction gap was completely ossified in the anterior skull base midline in all patients. Ossified pedicled flaps together with the skull base were thicker in patients than in controls at these two time points (p < 0.005 and p < 0.02). Patients with Pfeiffer syndrome had a significantly thicker skull base only and ossified pedicled flaps together with the skull base thicknesses (p = 0.01 and p = 0.03) and lower defect scores than patients with Crouzon or Apert syndrome (p = 0.03) 1 year postoperatively.

As ossification of the pedicled flaps and total reossification of the anterior skull base midline were observed in all patients, the authors indicate that performing pedicled flaps in frontofacial monobloc advancement surgery could promote the reossification of the anterior skull base.

Therapeutic, IV.

Restoring adequate blood supply is essential to the success of bone repair and augmentation procedures in craniofacial surgery. Nevertheless, the manner by which the incorporation of collagen gels (which can potentially induce angiogenesis), particulated deproteinized bovine bone grafts, or a combination of both can accelerate or delay bone regeneration in a clinical setting remains controversial. The objective of this study was to evaluate radiographically and histologically the capacity and functionality of particulated bone grafts and collagen gels on bone ossification and soft tissue formation in a rabbit calvarial defect. Bilateral calvarial defects in adult white New Zealand rabbits were filled or left either unfilled with bone grafts (DBBM), collagen gels (Gel), or a combination of both (DBBM + Gel). The defects were allowed to heal for 1, 2, and 6 months postoperatively before termination. Healing and regeneration patterns were assessed by 3D µCT and histological methods, and the biomechanical properties of regenerated tissue constructs were investigated and compared with autogenous calvarial bone. Results show that implanted DBBM and DBBM + Gel significantly enhanced immature bone formation compared with the empty and Gel groups; the latter treatment improved soft tissue formation and impeded immature bone formation but yielded no significant effect on mature bone formation. Implantation of DBBM not only effectively reconstructed 188.83 ± 25.25% of the tissue volume of the original defect, but it also regenerated bone tissue with similar tissue composition and biomechanical properties as the original autogenous bone. We also show that implanting different biomaterials can control the composition of soft and hard tissue in reconstructed tissue constructs in calvarial bone defects. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 529-544, 2019.

Many orthopaedic surgical procedures involve reattachment of a single tendon to bone. Whether tendon-to-bone healing is better facilitated by tendon fixation within a bone tunnel or on a cortical surface is unknown. The purpose of this study was to evaluate tendon-healing within a bone tunnel compared with that on the cortical surface in a rabbit model of biceps tenodesis.

Thirty-two rabbits (24 weeks of age) underwent unilateral proximal biceps tenodesis with tendon fixation within a bone tunnel (BT group) or on the cortical surface (SA [surface attachment] group). Postoperatively, rabbits were allowed free-cage activity without immobilization. All rabbits were killed 8 weeks after surgery. Healing was assessed by biomechanical testing, microcomputed tomography (micro-CT), and histomorphometric analysis.

Biomechanical testing demonstrated no significant difference between the groups in mean failure loads (BT: 56.8 ± 28.8 N, SA: 55.8 ± 14.9 N; p = 0.92) or stiffness (BT: 26.3 ± 16.6 N/mm, SA: 32.3 ± 9.6 N/mm; p = 0.34). Micro-CT analysis demonstrated no significant difference between the groups in mean volume of newly formed bone (BT: 69.3 ± 13.9 mm, SA: 65.5 ± 21.9 mm; p = 0.70) or tissue mineral density of newly formed bone (BT: 721.4 ± 10.9 mg/cm, SA: 698.6 ± 26.2 mg/cm; p = 0.07). On average, newly formed bone within the tunnel represented only 5% of the total new bone formed in the BT specimens. Histological analysis demonstrated tendon-bone interdigitation and early fibrocartilaginous zone formation on the outer cortical surface in both groups. In contrast, minimal tendon-bone bonding was observed within the tunnel in the BT specimens.

Tendon fixation in a bone tunnel and on the cortical surface resulted in similar healing profiles. For tendons placed within a bone tunnel, intratunnel healing was minimal compared with the healing outside the tunnel on the cortical surface.

The creation of large bone tunnels, which can lead to stress risers and increase the risk of fracture, may not be necessary for biceps tenodesis procedures.

The aim of this study was to present new a model that allows the study of the bone healing process, with an emphasis on the biological behavior of different graft-to-host interfaces. A standardized "over-inlay" surgical technique combined with a differential histomorphometric analysis is presented in order to optimize the use of critical-size calvarial defects in pre-clinical testing.

Critical-size defects were created into the parietal bone of 8 male Wistar rats. Deproteinized bovine bone (DBBM) blocks were inserted into the defects, so that part of the block was included within the calvarial thickness and part exceeded the calvarial height (an "over-inlay" graft). All animals were sacrificed at 1 or 3 months. Histomorphometric and immunohistochemical evaluation was carried out within distinct regions of interest (ROIs): the areas adjacent to the native bone (BA), the periosteal area (PA) and the central area (CA).

The animals healed without complications. Differential morphometry allowed the examination of the tissue composition within distinct regions: the BA presented consistent amounts of new bone formation (NB), which increased over time (24.53%±1.26% at 1 month; 37.73%±0.39% at 3 months), thus suggesting that this area makes a substantial contribution toward NB. The PA was mainly composed of fibrous tissue (71.16%±8.06% and 78.30%±2.67%, respectively), while the CA showed high amounts of DBBM at both time points (78.30%±2.67% and 74.68%±1.07%, respectively), demonstrating a slow remodeling process. Blood vessels revealed a progressive migration from the interface with native bone toward the central area of the graft. Osterix-positive cells observed at 1 month within the PA suggested that the periosteum was a source of osteoprogenitor elements. Alkaline phosphatase data on matrix deposition confirmed this observation.

The present model allowed for a standardized investigation of distinct graft-to-host interfaces both at vertically augmented and inlay-augmented sites, thus possibly limiting the number of animals required for pre-clinical investigations.

The purpose of this study is to investigate the potential of the systemic administration of different doses of rosuvastatin (RSV) on autogenous grafted critical-sized cortical bone defects. Twenty-four rats were divided into three groups: Group C (control), Group RSV-2 and Group RSV-5. A 5-mm diameter critical-size defect was created in the calvarium of each animal. In Group C, the defect was filled by autogenous graft only and rats were given saline solution with oral gavage for 28 days. In Group RSV-2 defects were filled with autogenous graft and rats were given 2 mg/kg rosuvastatin with oral gavage for 28 days. In Group RSV-5 defects were filled with autogenous graft and rats were given 5 mg/kg rosuvastatin with oral gavage for 28 days. All animals were euthanized at 28 days postoperative. Stereologic and micro-CT analyses were performed. New bone area (NBA) and connective tissue volumes were measured. Stereologic analysis showed that Group RSV-5 and RSV-2 had significantly more new bone at 4 weeks compared with group C. Connective tissue volumes were also significantly higher in RSV applicated groups. New bone and connective tissue volumes' difference were not statistically significant between RSV groups. Micro-CT results were similar with stereologic analyses. Orally administered RSV enhances bone regeneration in critical size calvarial rat defects filled with autogenous graft furthermore possible inflammatory effect should be investigated.

Pansynostosis can result in markedly thin calvarial bone resulting in poor quality and quantity of allograft for cranial vault expansion. Such scenarios can result in large calvarial defects and poorly stabilized constructs. Additionally, the osteoinductive properties of neonatal dura and paracranium in cranial vault reconstruction suggest the possibility of reconstructing extensive calvarial defects using minimal native calvarium given the appropriate scaffold. We report a case of subtotal cranial vault remodeling involving greater than 50% of the cranial vault using a custom poly DL lactic acid (Sonic Weld) resorbable plate construct and underlay calvarial bone grafting.

A 4-month-old male infant presented with a diagnosis of Cruzon syndrome and pansynostosis. Staged reconstruction was performed with the initial stage involving the posterior and middle cranial vault. Given the severity of the deformity, the native cranial bone was thinned with multiple defects such that it could not be used to provide structural integrity or sufficient surface coverage for cranial vault reconstruction. Useable bone comprised only a fraction of the surface area required to expand the posterior and midcranium. Resorbable poly DL lactic acid (Sonic Weld) plates were used to create a custom construct for reconstruction of the posterior and middle cranial vault. The construct was then seeded with usable fragments of the native calvarium and secured to the cranial base with resorbable pins.

The construct resulted in maintained cranial shape throughout the postoperative period. Postoperative computed tomography imaging demonstrated osteogenesis throughout the construct with bridging of the fragmented calvarial grafts. Examination of the construct during anterior cranial vault remodeling demonstrated near complete resorption of the construct, stable posterior cranial vault, and minimal dural adhesions to the posterior cranium. At 11 months postoperatively, the patient continues to demonstrate appropriate cranial expansion and maintenance of posterior cranial shape.

Fully resorbable constructs can provide effective structural support and a scaffold for osteogenisis in conjunction with minimal native calvarial bone grafts during reconstruction of large cranial vault defects in the infantile period.

The purpose of this study was to evaluate the effect of the periosteum attached to an iliac block bone graft on resorption of the grafted bone. Twenty-one rabbits were used. Iliac bone was harvested with (experimental group) or without a periosteum (control group) and grafted on the rabbit calvarium and fixed with miniscrews. The animals were killed, and specimens were harvested at 1, 4, and 8 weeks after the surgery. Histologic examination and histomorphometry were done. Grafted bones were severely resorbed, and the overall shapes were changed in the control group. On the contrary, the overall shape of the grafted bone was maintained, although the grafted bone was resorbed in the experimental group. Moreover, there were no osteoclasts adjacent to the periosteum of the graft. These results suggest that the periosteum attached to grafted bone can help establish early revascularization and prevent the resorption of grafted bone.

To compare the different resorption patterns between resorbable membrane barrier and periosteum after iliac block bone grafting radiographically and histologically.

Eighteen mature male rabbits weighing from 2.0 to 2.5 kg were used. The recipient site was the rabbit skull, and autogenous iliac bone was used as the grafting material. The harvested iliac block bones were divided in the following groups: autogenous iliac block bone with preservation of the periosteum (the periosteum group), autogenous iliac block bone covered with a resorbable collagen membrane (Biomesh®, Samyang Co, Korea) after removing the periosteum (the collagen membrane group), and autogenous iliac block bones with removal of the periosteum (the control group). In each experimental group, periosteum or resorbable collagen membrane of the donor site was fixed directed to the periosteum of the recipient site. The specimens were examined macroscopically, radiographically, histologically, and histomorphometrically at every 2, 4, and 8 weeks.

All groups presented excellent bone graft healing state without inflammation, dehiscence, or displacement. The radiolucency increased from mild to moderate in all groups over the experiment. The mean thickness of the upper end of the cortical iliac bone graft was statistically significantly different between the control group and the periosteum group, between the four-week and eight-week control group, and between the four- week and eight-week periosteum group (p & 0.05).

This study suggests that both the periosteum and the resorbable collagen membrane may help to prevent soft tissue infiltration into the bone graft and to reduce bone graft resorption compared to block graft alone.

There are some difficulties in approaching and removing the lesion in infratemporal fossa because of its anatomical location. After wide excision of tumor lesion, it is also difficult for reconstruction of mandibular condyle and cranium base on infratemporal fossa. Besides, there are some possibilities of cerebrospinal fluid leakage, intracranial infection and bone resorption. It is also challenging for functional reconstruction that allows normal mandibular movement, preventing mandibular condyle from invaginating into the skull. In this report, we present 14-month follow-up results of a patient who had undergone posterior segmental mandibulectomy including condyle and infratemporal calvarial bone and mandible reconstruction with free vascularized costochondral rib and calvarial bone graft to restoration of the temporomandibular joint area.

The purpose of this study is to: a) assess transport distraction to reconstruct cranial defects in radiated and non-radiated fields b) examine adipose grafting's effect on the bony regenerate and overlying wound, and c) elucidate sources of bone formation during transport distraction osteogenesis. Twenty-three male New Zealand white rabbits (3 months; 3.5 kg) were used, 10 non-irradiated and 13 irradiated (17 treatment, 6 control) with a one-time fraction of 35 Gy. A 16 × 16 mm defect was abutted by a 10 × 16 mm transport disc 5 weeks after irradiation, and 11 animals were fat grafted at the distraction site. Latency (1 day), distraction (1.5 mm/day), and consolidation (4 weeks) followed. Fluorochromes were injected subcutaneously and microCT, fluorescence, and histology assessed. In distracted animals without fat grafting, bone density measured 701.87 mgHA/ccm and 2271.95 mgHA/ccm in irradiated and non-irradiated animals. In distracted animals with fat grafting, bone density measured 703.23 mgHA/ccm and 2254.27 mgHA/ccm in irradiated and non-irradiated animals. Fluorescence revealed ossification emanating from the dura, periosteum, and transport segment with decreased formation in irradiated animals. Transport distraction is possible for cranial reconstruction in irradiated fields but short-term osseous fill is significantly diminished. Adipose grafting enhances wound healing in previously irradiated fields but does not enhance ossification.

Until recently, adverse effects of non-steroidal anti-inflammatory drugs (NSAIDs) on osseointegration of dental implants were unknown. Hence, this study investigated the short- and long-term effects of a 7-day regimen of parecoxib and diclofenac sodium on osseointegration of dental implants in calvarial bone.

Eighteen New Zealand White rabbits were randomly allocated into three groups (each n = 6): Control group with no postoperative pain killers (Group A), diclofenac group (Group B) and parecoxib group (Group C). In each animal, one dental implant was placed into the calvarial bone (total n = 18). Three rabbits from each group were sacrificed in Week 4. The other three rabbits from each group were sacrificed in Week 12 postoperatively. The implant together with the calvarial bone and dura mater was harvested and subjected to micro-computed tomography (micro-CT) and histomorphometric analysis.

Quantitative analysis of micro-CT data and histomorphometric data neither revealed any statistically significant (P ≤ 0.05) differences between the three different groups related to osseointegration nor between different time points of observation.

In rabbits, a 7-day regimen of appropriate doses of diclofenac sodium and parecoxib did not adversely affect osseointegration of dental implants and bone healing in calvaria, neither short nor long term (12 weeks).

Nonvascularized autologous bone grafts are the criterion standard in craniofacial reconstruction for bony defects involving the craniofacial skeleton. The authors have previously demonstrated that graft microarchitecture is the major determinant of volume maintenance for both inlay and onlay bone grafts following transplantation. This study performs a head-to-head quantitative analysis of volume maintenance between inlay and onlay bone grafts in the craniofacial skeleton using a rabbit model to comparatively determine their resorptive kinetics over time.

Fifty rabbits were divided randomly into six experimental groups: 3-week inlay, 3-week onlay, 8-week inlay, 8-week onlay, 16-week inlay, and 16-week onlay. Cortical bone from the lateral mandible and both cortical and cancellous bone from the ilium were harvested from each animal and placed either in or on the cranium. All bone grafts underwent micro-computed tomographic analysis at 3, 8, and 16 weeks.

All bone graft types in the inlay position increased their volume over time, with the greatest increase in endochondral cancellous bone. All bone graft types in the onlay position decreased their volume over time, with the greatest decrease in endochondral cancellous bone. Inlay bone grafts demonstrated increased volume compared with onlay bone grafts of identical embryologic origin and microarchitecture at all time points (p < 0.05).

Inlay bone grafts, irrespective of their embryologic origin, consistently display less resorption over time compared with onlay bone grafts in the craniofacial skeleton. Both inlay and onlay bone grafts are driven by the local mechanical environment to recapitulate the recipient bed.

The use of rabbits for experimental research has a long historical tradition. The aim of this review consists in outlining the use of the rabbit for research in implant dentistry and related tissue regeneration. Rabbits appear as a first-hand choice for fundamental implant design studies because of their size, easy handling, short life span, and economical aspects in purchasing and sustaining. In the following, the various anatomical sites in the rabbit will be summarized to provide an overview of current possibilities and limitations of this model for bone research in oral implantology.

Human adipose-derived stromal cells (hASCs) have a proven capacity to aid in osseous repair of calvarial defects. However, the bone defect microenvironment necessary for osseous healing is not fully understood. In this study, we postulated that the cell-cell interaction between engrafted ASCs and host dura mater (DM) cells is critical for the healing of calvarial defects. hASCs were engrafted into critical sized calvarial mouse defects. The DM-hASC interaction was manipulated surgically by DM removal or by insertion of a semipermeable or nonpermeable membrane between DM and hASCs. Radiographic, histologic, and gene expression analyses were performed. Next, the hASC-DM interaction is assessed by conditioned media (CM) and coculture assays. Finally, bone morphogenetic protein (BMP) signaling from DM was investigated in vivo using novel BMP-2 and anti-BMP-2/4 slow releasing scaffolds. With intact DM, osseous healing occurs both from host DM and engrafted hASCs. Interference with the DM-hASC interaction dramatically reduced calvarial healing with abrogated BMP-2-Smad-1/5 signaling. Using CM and coculture assays, mouse DM cells stimulated hASC osteogenesis via BMP signaling. Through in vivo manipulation of the BMP-2 pathway, we found that BMP-2 plays an important role in DM stimulation of hASC osteogenesis in the context of calvarial bone healing. BMP-2 supplementation to a defect with disrupted DM allowed for bone formation in a nonhealing defect. DM is an osteogenic cell type that both participates in and stimulates osseous healing in a hASC-engrafted calvarial defect. Furthermore, DM-derived BMP-2 paracrine stimulation appears to play a key role for hASC mediated repair.

Despite a wide range of available sources for bone repair, significant limitations persist. To bioengineer bone, we have previously transferred adenovirus-mediated human BMP-2 gene into autologous bone marrow stromal cells (MSC). We have successfully repaired large, full thickness, cranial defects using this approach. We report now the effectiveness of various hydrogels as the scaffold for this type of bone regeneration, comparing specifically alginate with Type I collagen. Cultured MSC of miniature swine were infected with BMP-2 or beta-gal adenovirus 7 days before implantation. These cells were mixed with alginate, ultrapure alginate, alginate-RGD, or type I collagen to fabricate the MSC/biomaterial constructs. The results of cranial bone regeneration were assessed by gross examination, histology, 3D CT, and biomechanical tests at 6 weeks and 3 months after implantation. We found that the BMP-2 MSC/collagen type I construct, but not the beta-gal control, effectively achieved nearly complete repair of the cranial defects. No bone regeneration was observed with the other hydrogels. Biomechanical testing showed that the new bone strength was very close and only slightly inferior to that of normal cranial bone. Controlling for the integration of stem cells and ex vivo gene transfer, the alginate scaffolds has a significant negative impact on the success of the construct. Our study demonstrates better bone regeneration by collagen type I over alginate. This may have therapeutic implications for tissue engineered bone repair.

Anterior cruciate ligament reconstruction with a soft tissue autograft (hamstring autograft) has grown in popularity in the last 10 years. However, the issues of a relatively long healing time and an inferior histological healing result in terms of Sharpey-like fibers connection in soft tissue grafts are still unsolved. To obtain a promising outcome in the long run, prompt osteointegration of the tendon graft within the bone tunnel is essential. In recent decades, numerous methods have been reported to enhance osteointegration of soft tissue graft in the bone tunnel. In this article, we review the current literature in this research area, mainly focusing on strategies applied to the local bone tunnel environment. Biological strategies such as stem cell and gene transfer technology, as well as the local application of specific growth factors have been reported to yield exciting results. The use of biological bone substitute and physical stimulation also obtained promising results. Artificially engineered tissue has promise as a solution to the problem of donor site morbidity. Despite these encouraging results, the current available evidence is still experimental. Further clinical studies in terms of randomized control trial in the future should be conducted to extrapolate these basic science study findings into clinical practice.

This study was designed to evaluate the bone regeneration potential of the dura mater and dura mater substitute (Durepair) in the presence of recombinant human bone morphogenetic protein-2 (rhBMP-2) delivered in a collagen sponge-collagen-ceramic matrix (CCM; MasterGraft Matrix) in a large skull defect in growing canines.

Forty immature male beagles were used to create two 2.5 x 4-cm cranial defects on each side of the sagittal suture. The dura mater on the left side was cut to make a 1 x 3-cm defect and replaced with bovine skin collagen (Durepair). The dura mater on the right side remained intact. Different doses of rhBMP-2 (none [8 animals], 0.11 mg/ml [4 animals], 0.21 mg/ml [4 animals], and 0.43 mg/ml [8 animals]) were infused on 2 Type I bovine absorbable collagen sponge (ACS) strips. The strips were layered with the CCM (15% hydroxyapatite [HA]/85% tricalcium phosphate [TCP]) to reconstruct both cranial defects. In a fifth group (8 animals), 0.43 mg/ml rhBMP-2 was directly infused into the CCM. Demineralized canine cancellous freeze-dried demineralized bone matrix (DBM; 8 animals) was used as a control in a sixth group. All materials were fixed under 2 resorbable protective sheets (MacroPore). Skulls were resected 16 weeks after operation. Histological and histomorphometric analyses on the percentage of the defect spanned by bone, and the percentage of residual HA-TCP granules and collagen were analyzed.

Calcified seroma was the only complication observed and only occurred in the 0.43-mg/ml rhBMP-2 groups (Groups 4 and 5). Dura mater repair appeared complete at 4 months in all animals. New bone was formed sporadically throughout the skull defect in the ACS+CCM and DBM groups without rhBMP-2. In all rhBMP-2 groups, mature new bone (compact and trabecular) was uniformly formed across the defect on both the repaired and intact dura mater sides. There was significant new compact bone formation on top of the repaired dura mater, which did not appear in the ACS+CCM and DBM groups lacking rhBMP-2. Greater HA-TCP and collagen scaffold resorption was noted in rhBMP-2 groups compared with non-rhBMP-2 groups. Statistical analysis showed there was a significantly lower percentage of bone spanning the defect in the ACS+CCM group compared with groups with rhBMP-2, with more residual HA-TCP and collagen on the repaired dura mater side than the intact dura mater side (p < 0.05). In all rhBMP-2 groups, there were no significant differences in new bone formation between the repaired and intact dura mater sides (p > 0.05).

The ACS+CCM combination had an effect similar to demineralized bone-on-bone regeneration in craniofacial reconstruction. The addition of rhBMP-2 to CCM directly or with ACS induces mature new bone formation in large cranial defects both in the presence of intact dura mater and repaired dura mater.

The aims of this study were to test whether or not the application of an in situ-formed synthetic polyethylene glycol hydrogel (PEG) used as a biodegradable membrane for guided bone regeneration with a variety of graft materials and ambient oxygen or hyperbaric oxygen (HBO) environments would result in enhanced bone regeneration, and to observe the histologic and histomorphometric aspects of bone healing of the calvarial defects with and without a PEG membrane.

Thirty adult, skeletally mature, male New Zealand white rabbits were randomly divided into 3 groups of 10 animals each. Bilateral 15-mm-diameter critical-size defects were created in the parietal bones of each animal. Group 1 served as a control with unfilled bilateral calvarial defects, group 2 had bilateral calvarial defects filled with morcelized autogenous calvarial bone, and group 3 had bilateral calvarial defects filled with a biphasic calcium phosphate ceramic. One of the calvarial defects was randomly protected with a PEG resorbable liquid membrane in each animal. Five animals from each group underwent a course of HBO treatment (2.4 ATA 100% oxygen for 90 minutes 5 days a week for 4 weeks) and the other 5 served as control and did not receive any supplemental oxygen (normobaric). The animals were killed 6 weeks after their surgery, and their parietal bones were harvested. The specimens were analyzed with microscopic computerized tomography (microCT) scans and histomorphometrics.

The unfilled normobaric control bony defects did not heal, proving the critical-size nature of these defects. The presence of autogenous bone or bone ceramic in the defects increased the bone volume fraction and bone mineral density of the defects (P < .001). The presence of a membrane in the ungrafted and autogenous bone grafted defects resulted in a decrease in the corrected bone volume fraction (P = .002) but not in the bone ceramic grafted defects (P = .580). Bony healing of defects where the membrane was unsupported was compromised; the membrane did not maintain the desired bone regeneration volume with the unfilled and autogenous bone grafted groups. The PEG resorbable liquid membrane worked best with the bone ceramic material. HBO did not ameliorate the healing of the autogenous bone graft or ceramic filled defects in the 6-week time period of this study.

Although the PEG resorbable liquid membrane is easy to use and forms an occlusive layer, caution is recommended when using the membrane over an unsupported defect. HBO did not ameliorate bony healing with the membrane at the early 6-week time point. The authors recommend future assessment with HBO at the 12-week time point.

During rotator cuff repair surgery, fixation and incorporation of ruptured rotator cuff tendon into the bone is a major concern. The repair usually fails at the tendon-bone interface, especially in cases where the tear is massive. The periosteum contains multipotent stem cells that have the potential to differentiate into osteogenic and chondrogenic tissues, which may restore the original structure at the tendon-bone interface, fibrocartilage. In this study, we investigated the effect of periosteum on the healing of the infraspinatus tendon and bone using a clinically relevant rabbit model of rotator cuff tear. We used 36 skeletally mature New Zealand white rabbits in the study. The infraspinatus tendon at right limb was detached from greater tuberosity, and a periosteal flap taken from the proximal tibia was sutured onto the torn end of tendon. The contralateral limb, which was used as a control, received the same treatment without a periosteum. The rabbits were sacrificed at 4, 8, and 12 weeks, and the tendon-bone interface was put to histological exam and the biomechanical testing to assess strength of tendon-bone interface. Histological analysis of the tendon-bone interface revealed that the periosteum formed a fibrous layer over the interface between tendon and bone. At 4 weeks, fibrotic tissue showed progressive integration over the interface between cuff tendon and bone. At 8 weeks, progressive formation of fibrovascular tissue and fibrocartilage was observed between tendon and bone. At 12 weeks, extensive formation of fibrocartilage and bone was noted in the interface. The significant increase of failure load with time indicated a progressive increase in the tendon-bone incorporation strength. At 4 weeks after operation, the attachment strength of the limbs with the periosteum treated was higher than that of the control limbs; however, this difference was not statistically significant. At 8 and 12 weeks, a statistically significant increase was noted in the attachment strength of the limb treated with the periosteum. Most specimens failed at the tendon-bone interface (18/20). In the treatment of a torn rotator cuff in rabbit model, improved healing process with greater attachment strength could be achieved by suturing the periosteum between the end of tendon and the bone trough. Histological examination revealed that the cambium layer of the periosteum could serve as a potent interface layer and become progressively mature and organized during the healing process, resulting in fibrocartilage formation and the subsequent integration of the disrupted tendon into the bone. Biomechanical testing revealed a progressive increase in the attachment strength with time indicating the progressive tendon-bone incorporation. When performing rotator cuff repair in a large or massive tear, a periosteal flap can be sutured onto the torn end of tendon to enhance tendon-bone healing.

Children less than 2 years of age are capable of healing large calvarial defects, whereas adults have been found to lack this endogenous ability. In this study, we used microarray analysis to compare genomewide expression patterns during active regeneration after injury with calvaria in skeletally immature and mature mice. Parietal bone defects were created in 6-day-old (juvenile) and 60-day-old (adult) mice using a 4-mm trephine bit (n = 20 mice per age group). The calvarial disc was removed, leaving the underlying dura mater intact. Two weeks after injury, the region of regeneration with the underlying dura mater was harvested, and RNA was extracted for microarray analysis. The 25 most differentially upregulated genes in juvenile regenerates compared with adults were listed, as well as selected bone-related genes. In addition, QRT-PCR confirmation of specific genes was performed for validation. Juvenile regenerates expressed significantly greater amounts of BMP-2, -4, -7, as well as FGF-2 and its receptor FGFR-1. Various other growth factors were also noted to be upregulated, including IGF-2 and Ptn. This corresponded with the increased expression of markers for osteogenic differentiation of Sparc and Oc. Markers of osteoclast activity, Acp5, Ctsk, and Mmp2, were noted to be greater in juvenile regenerates compared with adults. The observation of Mmp14 upregulation, however, highlights the importance of balanced osteoclast-mediated bone resorption for ultimate healing. The 2 most differentially regulated genes, transthyretin (Ttr) and prostaglandin D2 synthase (Ptgds), highlight the potential role of retinoic acid signaling and the prostaglandin axis on skeletal regeneration. These findings underscore the multitude of biomolecular mechanisms at play, allowing juvenile calvaria to heal after injury. The identification of various growth factors and cytokines involved also suggests novel therapeutic strategies for tissue-engineering purposes.

Tissue-engineered solutions for promoting the tendon graft incorporation within the bone tunnel appear to be promising.

To determine the feasibility that conjugation of hyaluronic acid-tethered bone morphogenetic protein-2 can be used to stimulate periosteal progenitor cells direct fibrocartilagenous attachment and new bone formation in an extra-articular tendon-bone healing model.

Controlled laboratory study.

A total of 42 mature New Zealand White rabbits were used. The long digitorum extensor tendon was transplanted into a bone tunnel of the proximal tibia. The tendon was pulled through a drill hole in the proximal tibia and attached to the medial aspect of the tibia. Photopolymerizable hydrogel based on poly (ethylene glycol) diacrylate with hyaluronic acid-tethered bone morphogenetic protein-2 was injected and photogelated in a bone tunnel. Histological and biomechanical examination of the tendon-bone interface was evaluated at postoperative weeks 3 and 6.

Histological analysis showed an interface fibrocartilage and new bone formed by photoencapsulation of bone morphogenetic protein-2 and periosteal progenitor cells at 6 weeks. Biomechanical testing revealed higher maximum pullout strength and stiffness in experimental groups with a statistically significant difference at 3 and 6 weeks after tendon transplantation.

The healing tendon-bone interface undergoes a gradual remodeling process; it appears that photoencapsulation of bone morphogenetic protein-2 and periosteal progenitor cells possesses a powerful inductive ability between the tendon and the bone to incorporate the healing in a rabbit model.

Novel technologies, such as those described in this study, including photopolymerization and tissue engineering, may provide minimally invasive therapeutic procedures via arthroscopy to enhance biological healing after reconstruction of the anterior cruciate ligament.

The geometric configuration of the skull is complex and unique to each individual. This study provides a new technique to define the outline of skull profile and attempt to find the common factors defining the ultimate skull configuration in adult population. Ninety-three lateral skull x-ray from the computed tomographic scan films were selected and digitized. The lateral skull surface was divided into 3 regions based on the presumed location of the coronal and lambdoid sutures. Three main curvatures (frontal, parietal, occipital) were consistently identified to overlap the skull periphery. The radius, cord length, and inclination of each curvature were measured. The average values for 3 defined curvatures of the skull profile were recorded. Factor analysis of the measured values produced 3 factors explaining the skull profile. The first factor explained 32% of total variance and was related to the overall size of the head as represented by total length and the radius of the curvature in the vertex and back of the head. The second factor covered 26% of the variance representing the inverse correlation between the angle of the frontal and parietal curves. The third factor revealed the direct correlation of the occipital and parietal angle. In all of these factors, the frontal zone variation was independent or opposite of the parieto-occipital zone. A strong association between the total length of the skull, occipital curve radius, and length with the sex was shown. In conclusion, the skull profile topography has large variation and can be defined mathematically by 2 distinct territories: frontal and parieto-occipital zones. These territories hinge on the coronal suture. Therefore, the coronal suture may play a dominant role in final skull configuration.

Apert syndrome (AS), a severe form of craniosynostosis, is caused by dominant gain-of-function mutations in FGFR2. Because the periosteum contribution to AS cranial pathophysiology is unknown, we tested the osteogenic potential of AS periosteal cells (p.Ser252Trp mutation) and observed that these cells are more committed toward the osteoblast lineage. To delineate the gene expression profile involved in this abnormal behavior, we performed a global gene expression analysis of coronal suture periosteal cells from seven AS patients (p.Ser252Trp), and matched controls. We identified 263 genes with significantly altered expression in AS samples (118 upregulated, 145 downregulated; SNR >or= |0.4|, P <or= 0.05). Several upregulated genes are involved in positive regulation of cell proliferation and nucleotide metabolism, whereas several downregulated genes are involved in inhibition of cell proliferation, gene expression regulation, cell adhesion, and extracellular matrix organization, and in PIK3-MAPK cascades. AS expression profile was confirmed through real-time PCR of a selected set of genes using RNAs from AS and control cells as well as from control cells treated with high FGF2 concentration, and through the analysis of genes involved in FGF-FGFR signaling. Our results allowed us to: (a) suggest that AS periosteal cells present enhanced osteogenic potential, (b) unravel a specific gene expression signature characteristic of AS periosteal cells which may be associated with their osteogenic commitment, (c) identify a set of novel genes involved in the pathophysiology of AS or other craniosynostotic conditions, and (d) suggest for the first time that the periosteum might be involved in the pathophysiology of AS.

Apert syndrome (AS), a severe form of craniosynostosis, is caused by dominant gain-of-function mutations in FGFR2. Because the periosteum contribution to AS cranial pathophysiology is unknown, we tested the osteogenic potential of AS periosteal cells (p.Ser252Trp mutation) and observed that these cells are more committed toward the osteoblast lineage. To delineate the gene expression profile involved in this abnormal behavior, we performed a global gene expression analysis of coronal suture periosteal cells from seven AS patients (p.Ser252Trp), and matched controls. We identified 263 genes with significantly altered expression in AS samples (118 upregulated, 145 downregulated; SNR >or= |0.4|, P <or= 0.05). Several upregulated genes are involved in positive regulation of cell proliferation and nucleotide metabolism, whereas several downregulated genes are involved in inhibition of cell proliferation, gene expression regulation, cell adhesion, and extracellular matrix organization, and in PIK3-MAPK cascades. AS expression profile was confirmed through real-time PCR of a selected set of genes using RNAs from AS and control cells as well as from control cells treated with high FGF2 concentration, and through the analysis of genes involved in FGF-FGFR signaling. Our results allowed us to: (a) suggest that AS periosteal cells present enhanced osteogenic potential, (b) unravel a specific gene expression signature characteristic of AS periosteal cells which may be associated with their osteogenic commitment, (c) identify a set of novel genes involved in the pathophysiology of AS or other craniosynostotic conditions, and (d) suggest for the first time that the periosteum might be involved in the pathophysiology of AS.

Although reossification of large calvarial defects is possible in children, adults lack this tissue engineering capacity. In this study, the authors compared the differences in gene expression between juvenile and adult dura mater using a mouse cDNA microarray with 42,000 unique elements.

Non-suture-associated parietal bone was harvested from 6-day-old and 60-day-old mice. The dura mater was carefully dissected from the calvarial disk and snap-frozen. RNA was extracted from pooled dura mater for microarray analysis. The 25 most differentially expressed genes were listed, as were selected bone-related genes. In addition, quantitative real-time reverse-transcriptase polymerase chain reaction confirmation of selected genes-BMP-2, BMP-4, and BMP-7; and osteopontin (OP), osteocalcin (OC), and FGFR-1-was performed.

Juvenile dura mater expressed significantly greater amounts of BMP-2 and OP. Minimal difference in OC expression was observed between juvenile and adult dura mater. Extracellular matrix proteins (Col3a1, 5a1, 6a1, and fibronectin 1), osteoblast differentiation markers (Runx2/Cbfa1, Itm2a, and FGFR-1), and the growth factor Ptn were among other genes with greater expression in juvenile dura mater. Markers of osteoclasts (Acp5, MMP9, Ctsk) and the multiple candidate gene Ntrk2 were also expressed at higher levels in the juvenile dura mater.

These findings suggest a more differentiated osteoprogenitor population to exist along with a greater presence of osteoclasts in the juvenile dura mater relative to adults. In addition to establishing a baseline difference in gene expression between juvenile and adult dura mater, new genes potentially critical to the regenerative potential of juvenile calvaria were identified.

Autogenous bone grafting is considered the standard in management of bony defects but has some disadvantages, including limited source of graft material, especially in children. This study represents an attempt to regenerate bone at the donor site of iliac bone grafts using the guided bone regeneration principle for future use in multistage bone reconstruction by grafting.

Critical size defects were created in 24 iliac bones of 12 skeletally mature New Zealand White rabbits. Defects in group 1 (n = 12) were covered with inverted U-shaped resorbable mesh (space maintainer) and polytetrafluoroethylene membranes underneath the periosteum. In group 2 (n = 6), inverted U-shaped resorbable mesh was used alone (positive control). In group 3 (n = 6), neither resorbable mesh nor polytetrafluoroethylene membranes were used (negative control). An unpaired t test was used for comparison between each two groups.

Plain radiographs and contact microradiographic studies showed that bone regeneration was significantly higher in group 1 and group 2 than in group 3 (p < 0.001). There was no significant difference between group 1 and group 2 regarding density.

The periosteum acted as an ideal membrane for guided bone regeneration so that the polytetrafluoroethylene membranes could be used only to compensate for the deficient periosteum. Space maintenance was essential for bone regeneration.

Bone reconstruction in the head and neck region is frequently performed in the context of previous radiation treatment. Thus, the effectiveness of tissue engineering approaches for regenerating bone in radiated defects needs to be determined before considering application to patients. Incomplete healing is described when using osteoinductive protein therapy alone for bone defects previously treated with radiation. We hypothesized that a different approach using ex vivo gene therapy can heal these severely compromised defects.

Animal study using Fisher rats.

Two weeks before surgery, rats received either no radiation or a 12 Gray radiation dose to the calvarium. Syngeneic dermal fibroblasts were transduced ex vivo using an adenoviral vector containing the cDNA for bone morphogenetic protein (BMP)-7. Critical-sized calvarial defects were created, and either a transduced cell-seeded scaffold or an autologous bone graft was placed into the defect. Nonradiated defects were harvested 4 weeks later for both groups. Radiated defects treated with bone grafts were harvested at 4 weeks, and those treated with gene therapy were harvested either at 4 or 8 weeks. Gross inspection and histology were used to evaluate wound healing.

None of the bone grafts had gross or histologic evidence of healing at the wound margins. The nonradiated gene therapy treated defects revealed gross and histologic near-100% bone regeneration by 4 weeks after surgery. By gross inspection, the radiated defects had soft tissue admixed with islands of bone at both 4 and 8 weeks. The histologic appearance revealed areas of dense bone in a nonconfluent pattern admixed with adjacent cells having the morphologic appearance of hypertrophic chondrocytes, suggesting continued endochondral ossification.

Preoperative radiation significantly impairs the ability of BMP-7 ex vivo gene therapy to heal rat critical-sized cranial defects. This finding has significant implications for translating this tissue engineering approach to patients with cancer-related segmental bone defects.

Tendon-bone incorporation of a tendon graft within the bone tunnel is of priority concern when using for anterior cruciate ligament (ACL) reconstruction. Superior healing process and stronger healing strength can be achieved when periosteum is sutured on the tendon inserted into a bone tunnel. We applied this idea to ACL reconstruction for enhancing tendon graft-bone tunnel healing. This is a prospective clinical outcome study with this surgical technique at minimal 2 years follow-up. Periosteum-enveloping hamstring tendon graft has been used in 68 patients. Data from 62 patients who had been followed up completely were analyzed. All patients suffered from a grade 3 or higher grade of Lachman and anterior drawer test with a positive pivot-shift test. Clinical assessments included the Lysholm knee scores, International Knee Documentation Committee (IKDC) scores, KT-1000 instrumented testing, thigh muscle assessment, and radiographic evaluation. The median Lysholm knee score was 59 (40-70) and 94 (60-100) points (P<0.01) before and after surgery. After reconstruction, 81% of patients were able to return to moderate or strenuous activity. Four (6%) patients were found to exhibit grade 2 or more ligament laxity. Complete range of motion could be achieved in 86% of patients. Three patients (5%) had positive pivot shift. Finally, 92% of patients were assessed as normal or nearly normal rating by IKDC guideline. Bone tunnels enlargement of more than 1 mm was identified in 5% of femoral tunnels and 6% of tibial tunnels. The study shows that a satisfactory result can be achieved with the periosteum-enveloping hamstring tendon graft in ACL reconstruction. Periosteum can be easily harvested at the proximal tibia from a routine incision for hamstring tendon harvesting. Besides the potential for improving tendon-bone healing, enveloped periosteum may help to seal the intra-articular tunnel opening in the early postoperative period, and thus avoid synovial fluid reflux into the tunnel. Bone tunnel enlargement could be reduced.